Lieber Sonja, Reinartz Silke, Raifer Hartmann, Finkernagel Florian, Dreyer Tobias, Bronger Holger, Jansen Julia M, Wagner Uwe, Worzfeld Thomas, Müller Rolf, Huber Magdalena
Institute of Molecular Biology and Tumor Research, Center for Tumor Biology and Immunology, Philipps University Marburg, Marburg, Germany.
Clinic for Gynecology, Gynecological Oncology and Gynecological Endocrinology, Center for Tumor Biology and Immunology (ZTI), Philipps University Marburg, Marburg, Germany.
Oncoimmunology. 2018 Mar 15;7(5):e1424672. doi: 10.1080/2162402X.2018.1424672. eCollection 2018.
The accumulation of intratumoral CD8 T cells is associated with the survival of high grade serous ovarian carcinoma patients, but it is unclear which CD8 T cell subsets contribute to this effect and how they are affected by the peritoneal tumor microenvironment. Here, we provide evidence for a functional link between long relapse-free survival, accumulation of CD8 effector memory T (T) cells in peritoneal effusion (ascites), and the level of the CD8 T attracting chemokine CXCL9, produced by macrophages as a major source. We also propose a novel mechanism by which the tumor microenvironment could contribute to T cell dysfunction and shorter survival, i.e., diminished expression levels of essential signaling proteins, including STAT5B, PLCγ1 and NFATc2. CD8 T cells in ascites, CXCL9 levels and the expression of crucial signal transduction proteins may therefore be important biomarkers to gauge the efficiency of immune therapies and potentially represent therapeutic targets.
肿瘤内CD8 T细胞的积累与高级别浆液性卵巢癌患者的生存相关,但尚不清楚哪些CD8 T细胞亚群促成了这种效应以及它们如何受到腹膜肿瘤微环境的影响。在此,我们提供了证据,证明长期无复发生存、腹膜积液(腹水)中CD8效应记忆T(Teff)细胞的积累以及巨噬细胞作为主要来源产生的CD8 T细胞趋化因子CXCL9水平之间存在功能联系。我们还提出了一种新机制,肿瘤微环境可能通过该机制导致T细胞功能障碍和生存期缩短,即包括STAT5B、PLCγ1和NFATc2在内的关键信号蛋白表达水平降低。因此,腹水中的CD8 T细胞、CXCL9水平和关键信号转导蛋白的表达可能是衡量免疫治疗效果的重要生物标志物,并且有可能成为治疗靶点。